EFFECT OF SPIRONOLACTONE ON HEPATIC-MICROSOMAL MONO-OXYGENASE AND AZOREDUCTASE ACTIVITIES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 36  (1) , 87-103
Abstract
Spironolactone pretreatment (10 mg/100 mg, twice daily for 4 days, orally) caused a significant decrease in cytochrome P-450 levels in the liver microsomes in female rats, but male rats were unaffected. NADH oxidase activity was significantly decreased in both sexes by this pretreatment, but NADPH oxidase and NADH cytochrome c reductase activities were not altered. NADPH cytochrome c reductase activity was increased more markedly in female rats. Despite the decrease in P-450 while it remained unchanged in males. 7-Ethoxycoumarin O-deethylase activity was markedly increased in male and slightly decreased in female rats. The azoreductase activity was slightly reduced in treated male rats and remained unaltered in female rats when it was expressed in activity per milligram microsomal protein, but the activity did show a significant increase in female rats when it was expressed as a P-450 specific rate. Sex-associated differences in the effect of spironolactone on the rat liver microsomal drug metabolizing enzyme system cannot be simply explained by the effect on adrenal and testicular steroids in male rats. It seems unlikely that these effects were caused by an alteration in P-450 quality by selective destruction of certain species of P-450.

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